Mitochondria play fundamental role in maintaining cellular metabolic homeostasis, and metabolic disorders including
type 2 diabetes (T2D) have been associated with
mitochondrial dysfunction. Pathophysiological mechanisms are coupled to increased production of
reactive oxygen species and oxidative stress, together with reduced bioactivity/signaling of
nitric oxide (NO). Novel strategies restoring these abnormalities may have therapeutic potential in order to prevent or even treat T2D and associated cardiovascular and renal co-morbidities. A diet rich in green leafy vegetables, which contains high concentrations of inorganic
nitrate, has been shown to reduce the risk of T2D. To this regard research has shown that in addition to the classical
NO synthase (NOS) dependent pathway,
nitrate from our diet can work as an alternative precursor for NO and other bioactive
nitrogen oxide species via serial reductions of
nitrate (i.e.
nitrate-
nitrite-NO pathway). This non-conventional pathway may act as an efficient back-up system during various pathological conditions when the endogenous NOS system is compromised (e.g. acidemia,
hypoxia,
ischemia, aging, oxidative stress). A number of experimental studies have demonstrated protective effects of
nitrate supplementation in models of
obesity,
metabolic syndrome and T2D. Recently, attention has been directed towards the effects of
nitrate/
nitrite on mitochondrial functions including beiging/browning of white adipose tissue, PGC-1α and
SIRT3 dependent AMPK activation, GLUT4 translocation and mitochondrial fusion-dependent improvements in
glucose homeostasis, as well as dampening of
NADPH oxidase activity. In this review, we examine recent research related to the effects of bioactive
nitrogen oxide species on mitochondrial function with emphasis on T2D.